Accepted Manuscript Title: An Epileptologist´es View: Seizure-related Outcomes after Radiofrequency Ablation for Mesial Temporal Lobe Epilepsy Authors: Zdenˇek Vojtˇech, Michaela Star´a PII: DOI: Reference:
S0920-1211(17)30229-2 http://dx.doi.org/10.1016/j.eplepsyres.2017.09.004 EPIRES 5804
To appear in:
Epilepsy Research
Received date: Revised date: Accepted date:
16-4-2017 27-6-2017 11-9-2017
Please cite this article as: Vojtˇech, Zdenˇek, Star´a, Michaela, An Epileptologist´es View: Seizure-related Outcomes after Radiofrequency Ablation for Mesial Temporal Lobe Epilepsy.Epilepsy Research http://dx.doi.org/10.1016/j.eplepsyres.2017.09.004 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
An Epileptologist´s View: Seizure-related Outcomes after Radiofrequency Ablation for Mesial Temporal Lobe Epilepsy Zdeněk Vojtěch, Michaela Stará Na Homolce Hospital Epilepsy Center; Prague, Czech Republic.
*
Corresponding author: Zdeněk Vojtěch, M.D, Ph.D.; Department of Neurology, Na Homolce
Hospital, Roentgenova 2, 150 30 Prague 5; E-mail address: [email protected] ; tel.+420 257272556; fax. +420 257273314
Highlights
SAHE destroys target structures only partially
In SAHE, seizure outcomes are comparable with open surgery
Seizure outcomes change only minimally over time
Summary In this article, we provide an overview of the reasons for the introduction of less invasive treatment modalities in the management of intractable mesial temporal lobe epilepsy (mTLE). We summarize our published research on stereotactic amygdalohippocampectomy (SAHE) and recalculate our data for the patients´ last visit. In our previous work, we found that patients achieved long-term seizurefree outcomes in 70.5%. Re-analysis of results in a subgroup of patient who were diagnosed and followed-up at Epilepsy Center, Na Homolce Hospital, Prague, indicate that these outcomes are
durable. Re-treatment in treatment failures was successful in all cases. The discussion compares novel treatment options and defines the place of SAHE among them. Key words Epilepsy surgery, stereotactic amygdalohippocampectomy, minimally invasive surgery
1. Introduction Surgical treatment of mTLE by anterior temporal lobectomy (ATL) or amygdalohippocampectomy (AHE) is an established treatment method which renders most of the patients to be seizure-free (60– 80%) (Spencer and Huh, 2008). Postoperative surgical morbidity is low with permanent deficits in less than 2% of patients in most centers (Georgiadis et al., 2013). Thus, what are the reasons for introducing stereotactic methods in the treatment of mTLE? Current surgical methods are based on the complete destruction of target structures (hippocampus, amygdala and parahippocampal gyrus). However, these operations frequently transect white matter tracts and resect tissue which is not epileptogenic. Several approaches have been developed to minimize collateral damage (transsylvian, subtemporal, and transcortical amygdalohippocampectomy) (Bozkurt et al., 2016). However, even these modifications could be the cause of it (eg. due to vascular spasms or direct white matter tracts transection). Paradoxically, there is a questionable correlation between the extent of resection and seizure outcome. This fact was demonstrated not only for the extent of neocortical temporal resections but also for hippocampal length/volume reduction (Schramm, 2008). Furthermore, the planned and real extent of the resection may differ (Schramm et al., 2011). In mTLE, epilepsy surgery is underutilized, largely because of concerns about its invasive nature and adverse side-effects which cause attending physicians to be reluctant to refer their patients for
surgery and for the patients to accept it (Englot et al., 2016). This is one of the reasons to search for less invasive treatment techniques which should be at least equally effective as treatment options used so far and have some advantage over these methods (safety profile, better patients´ comfort or cost effectiveness). In mTLE, despite a widely distributed epileptogenic network involving temporal and extratemporal structures, the epileptogenic zone is relatively circumscribed. Intuitively, one may think that a seizure outcome should be the same irrespective of the method by which mesiotemporal target structures are destroyed. Besides established epilepsy microsurgery, current literature offers several alternatives: multiple hippocampal transections, radiosurgery, laser ablation, MRI-guided focused ultrasound ablation and SAHE (Quigg and Harden, 2014).
2. Material and methods We performed SAHE over the period between 2004–2010 (Liščák et al., 2010).Then we stopped to practice it as an original stereotactic probe (Neuro N50, Fischer-Leibinger, Germany) became unavailable. Seizure outcomes have been discussed in previous articles. The problem with reporting these results is that patients from several institutions were referred for the treatment. Therefore, pre-surgical evaluation protocols and their interpretation varied. This led to inhomogeneity of the group. Furthermore, even patients followed-up at Epilepsy Center, Na Homolce Hospital, Prague frequently did not fulfil inclusion criteria for individual studies. Therefore, numbers of included patients in specific studies varied. A previous paper described the unselected group of all 61 treated patients (Vojtěch et al., 2014). Our preoperative diagnostics was based largely on standard noninvasive protocols (MRI, FDG-PET, scalp video-EEG, neuropsychological assessment) (Vojtěch et al., 2015-a). Noninvasive data (unilateral ictal pattern onset, hippocampal sclerosis and hypometabolism) were fully concordant in 36 and partially concordant or incomplete in 22 cases. We used intracranial video EEG recordings (SEEG) in three
cases. In three patients, another potentially epileptogenic lesion was found. Despite incomplete convergence of all preoperative tests, mTLE was diagnosed in all patients. 3. Results 3.1 Outcome with respect to seizures At the time of seizure outcome analysis, the mean postoperative follow-up was 5.3 years. We found Engel Class scores as follows: 43 (70.5 %) Class I, six (9.8 %) Class II, nine (14.8 %) Class III, and three (4.9 %) Class IV. For insufficient seizure control, five patients (8.2%) were reoperated on. Open surgery was performed in three patients in whom full coverage of the target structures was not possible due to individual anatomy. They all became Engel IA after the operation. Re-thermolesion was performed in two cases in whom the extent of the first lesion was suboptimal. One patient became Class IA, the other Class IB. No statistically significant difference was found in epilepsy duration and age at the time of the operation between seizure-free and non-seizure-free patients (Class I vs. Classes II-IV). Although data from a smaller subgroup showed a tendency for a better outcome in patients with concordant preoperative results and those treated on the left (Malíková et al., 2012), seizure outcomes did not differ in patients with completely and incompletely congruent preoperative data in the whole group. These results seem to change little over time. In one study we described 35 patients, (27 treated on the left and eight on the right) with a follow-up longer than one year (Malíková et al., 2012). One year after the procedure, Engel Classes were as follows: Class I in twenty-seven patients (77%), Class II in five patients (14%), Class III in one (3%) and Class IV in 2 (6%). 26 of these patients were followed-up for more than 3 years. 20 (77%) of them were Class I, three (12%) Class II, one Class III (4%), and two Class IV (8%).
For this article, Engel Scores were re-calculated in a subgroup of 39 patients who were diagnosed and treated at Epilepsy Center, Na Homolce Hospital, Prague, and in whom their last follow-up visit was less than one year (Table 1). Table 1: FU, follow-up visit (numbers= years after treatment) 28 of these patients were treated on the left and 11 on the right side. They were followed-up with for a mean of 8.83 years (106 months) (median 9 years [108 months]), range 5.4-12.2 years (65-146 months). 2 years after surgery their Engel Score was 32 Engel I (16 Engel IA), 4 Engel II, 2 Engel III, 1 Engel IV. All these patients were followed-up for 6 years. Their seizure outcome was as follows: 33 Engel I (18 Engel IA), 2 Engel II, 3 Engel III, 1 Engel IV. At their last visit, they were classified: 32 Engel I (20 Engel IA), 3 Engel II, 3 Engel III, 1 Engel IV. However, only three of 61 patients were not taking antiepileptic drugs. Seizures relapsed in the other five patients in whom treatment was attempted to be discontinued. In most patients the drug burden was at least reduced. 3.2 Neuroradiological results
Neuroradiological follow-up demonstrated only partial destruction of target structures which varied in size. Mean hippocampal volume reduction was 58±17% on the left and 54±27% on the right side (Malíková et al., 2012). In a small study of 18 patients, Engel Class IA was found in eight of nine patients (89%) in whom both amygdalar and hippocampal volumes were reduced by more than half (Malíková et al., 2009). In patients where both structures were destroyed by less than 50%, Engel Class I was 67%. In other studies, no convincing correlation was found between the seizure outcome and amygdalar and hippocampal volume reduction (Malíková et al., 2009, 2010). No significant correlation was found between the volume reduction of perirhinal and entorhinal cortices to seizure outcome (Malíková et al., 2011).
In a study of 75 mTLE patients (Malíková et al., 2014), seizure outcome after SAHE was compared (n=41, 11 on the right, 30 on the left) and ATL (n= 34, 21 on the right, 13 on the left ). Two years after surgery, the proportion of seizure-free patients was almost the same: 79.3% after SAHE and 76.5% after ATL. However, volume reductions were smaller in SAHE than ATL (amygdalar 50.3 ± 21.9% vs. 80.2 ± 20.9%, hippocampal 60.6 ± 18.7% vs. 86.0 ± 12.7%, respectively).
4. Discussion
The follow briefly compares the basic principles of current alternatives to conventional epilepsy surgery. Multiple hippocampal transections are a minimally destructive modification of traditional epilepsy surgery. Unfortunately, it has usually been used together with other methods (multiple subpial transections or topectomies) (Usami et al., 2016). Thus, the benefit of this method is difficult to assess. Furthermore, some collateral damage cannot be avoided in both access routestranssylvian (Uda et al., 2016) and trans middle temporal gyrus (Patil and Andrews, 2013). Major disadvantages of radiosurgery are delayed antiseizure effects, collateral damage and early and late radiotoxic changes which warrant prolonged neuroimaging follow-up (Vojtěch et al., 2015-b). On the other hand, laser therapy is highly targeted with minimal collateral damage and acts immediately. However, it destroys target structures in a confluent way, albeit incompletely. Reported results are somewhat inferior to open surgery and optimal volume of destruction is a matter of further research (Kang et al., 2016). The idea of SAHE is not new. It was performed in the 70´s using pneumoencephalography for navigation. Its seizure outcome was comparable to open surgery (Vladyka, 1978). Contemporary improvement of the method lies in application of modern neuroimaging and navigation methods (Liščák et al., 2010). SAHE has the potential advantages of minimal collateral damage, partial and non-confluent destruction of target structures, and immediate seizure control. We speculate that the antiepileptic effect of SAHE may be mediated by preferential disconnection of longitudinal hippocampal fibers
through which seizure activity spreads. The hypothesis is that some residual neuronal circuits may reorganize and support memory. Our idea is as follows – to achieve seizure reduction, it is important to balance volume reduction and confluency of the lesion. This issue comes from studies of the London-Ontario group (Parrent and Blume, 1999). In their article, the authors divided their patients into two groups. In Group I, they performed limited numbers of discrete lesions (mean, 6.4) in shorter anteroposterior length of amygdalohippocampal complex (13-21 mm, mean, 16.8 mm). In Group II, they created more lesions (mean, 26) in more confluent fashion and longer length (15-34 mm, mean, 21.5 mm). They achieved favorable outcome more often in Group II compared to Group I (60% vs. 20%). Our hypothesis is that better seizure outcome in our patients may be explained by wider coverage of amygdalohippocampal complex (16-38 lesions, median, 25, 30-45 mm trajectory, median, 35). We must stress that the results do not suggest that SAHE is superior to open epilepsy surgery in respect to seizure outcome. There is no reason why it should. Neither does this research comment on the differences in epileptological results of SAHE and other alternatives (eg. laser ablations). These questions warrant further studies comparing various methods. However, it is possible that patients may benefit from balancing between selectivity and minimization of collateral damage in the neuropsychological domain and receive better comfort. The direct costs of SAHE and conventional epilepsy surgery were not compared. However, the fact that no postoperative intensive care is needed in uncomplicated cases, and shorter stay in the hospital show that it should be more cost effective than open surgery. Furthermore, the stereotactic probe is obviously less expensive than equipment for laser ablation. A specific shortcoming of SAHE is the low percentage of drug-free patients. The disadvantage of all alternative methods is that no material for histologic evaluation is available. 5. Conclusion
Current experience with SAHE is limited. It is based on the results of a single center which treated a small and highly non-homogenous group of patients. There is also a bias as most patients were treated on the language dominant side. However, the promising results warrant further evaluation, ideally by a multicenter randomized study comparing SAHE with conventional surgery or other alternative treatment methods. Using contemporary neuroimaging technology, these studies may uncover certain patient groups which could benefit most from the treatment (eg. various types of hippocampal sclerosis or MRI-negative cases) or for which SAHE is not suitable (eg. mTLE plus). References Bozkurt, B., da Silva Centeno, R., Chaddad-Neto, F., da Costa, M.D., Goiri, M.A., Karadag, A., Tugcu, B., Ovalioglu, T.C., Tanriover, N., Kaya, S., Yagmurlu, K., Grande, A., 2016. Transcortical selective amygdalohippocampectomy technique through the middle temporal gyrus revisited: An anatomical study laboratory investigation. J Clin. Neurosci. 34: 237-45. Englot, D.J., 2013. The persistent under-utilization of epilepsy surgery. Epilepsy Res. 118, 68-9. Georgiadis, I., Kapsalaki, E.Z., Fountas, K.N., 2013. Temporal lobe resective surgery for medically intractable epilepsy: a review of complications and side effects. Epilepsy Res. Treat. 752195. Kang, J.Y., Wu. C., Tracy, J., Lorenzo, M., Evans, J., Nei, M., Skidmore, C., Mintzer, S., Sharan, A.D., Sperling, M.R., 2016. Laser interstitial thermal therapy for medically intractable mesial temporal lobe epilepsy. Epilepsia. 57, 325-34. Liščák, R., Malíková, H., Kalina, M., Vojtěch, Z., Procházka, T., Marusič, P., Vladyka, V, 2010. Stereotactic radiofrequency amygdalohippocampectomy in the treatment of mesial temporal lobe epilepsy. Acta Neurochir (Wien). 152(8):1291-8. Malíková, H., Krámská, L., Liščák, R., Vojtěch, Z., Procházka, T., Marečková, I., Lukavský, J., Druga, R., 2012. Stereotactic radiofrequency amygdalohippocampectomy for the treatment of temporal lobe epilepsy: do good neuropsychological and seizure outcomes correlate with hippocampal volume reduction? Epilepsy Res. 102, 34-44.
Malíková, H., Krámská, L., Vojtěch, Z., Liščák, R., Šroubek, J., Lukavský, J., Druga, R., 2014. Different surgical approaches for mesial temporal epilepsy: resection extent, seizure, and neuropsychological outcomes. Stereotact. Funct. Neurosurg. 92, 372-80. Malíková, H., Vojtěch, Z., Liščák, R., Procházka, T., Vymazal, J., Vladyka, V., Keller, J., Kalina, M., 2009. Stereotactic radiofrequency amygdalohippocampectomy for the treatment of mesial temporal lobe epilepsy: correlation of MR with clinical seizure outcome. Epilepsy Res. 83, 235-242. Patil, A., Andrews R., 2013. Long term follow-up after multiple hippocampal transection (MHT). Seizure. 22:731-4. Parrent, A. G., Blume, W. T., (1999). Stereotactic amygdalohippocampotomy for the treatment of medial temporal lobe epilepsy. Epilepsia. 1999;40(10):1408-16. Quigg, M., Harden, C., 2014. Minimally invasive techniques for epilepsy surgery: stereotactic radiosurgery and other technologies. J. Neurosurg. 121 Suppl., 232-40. Spencer, S., Huh, L., 2008. Outcomes of epilepsy surgery in adults and children. Lancet Neurol. 7, 52537. Schramm, J., 2008. Temporal lobe epilepsy surgery and the quest for optimal extent of resection: a review. Epilepsia 49, 1296-307. Schramm, J., Lehmann, T.N., Zentner, J., Mueller, C.A., Scorzin, J., Fimmers, R., Meencke, H.J., Schulze-Bonhage A., Elger, C.E., 2011. Randomized controlled trial of 2.5-cm versus 3.5-cm mesial temporal resection-Part 2: volumetric resection extent and subgroup analyses. Acta Neurochir. (Wien) 153, 221-8. Uda, T., Morino, M., Ito, H., Minami, N., Hosono, A., Nagai, T., Matsumoto, T., (2013). Transsylvian hippocampal transection for mesial temporal lobe epilepsy: surgical indications, procedure, and postoperative seizure and memory outcomes. J Neurosurg. 119:1098-104. Usami, K., Kubota, M., Kawai, K., Kunii, N., Matsuo, T., Ibayashi, K., Takahashi, M., Kamada, K., Momose, T., Aoki, S., Saito, N., 2016. Long-term outcome and neuroradiologic changes after multiple
hippocampal transection combined with multiple subpial transection or lesionectomy for temporal lobe epilepsy. Epilepsia. 57, 931-40. Vladyka, V., 1978. Tactics in the surgical treatment epilepsy and its realization in cases of temporal epilepsy. Cesk Slov Neurol N 41:95–106. Vojtěch, Z., Malíková, H., Krámská, L., Anýž, J., Syrůček, M., Zámečník, J., Liščák, R., Vladyka, V., 2014. Long-term seizure outcome after stereotactic amygdalohippocampectomy. Acta Neurochir. (Wien) 156, 1529-37. Vojtěch, Z., Malíková, H., Krámská, L., Liščák, R., Vladyka, V, 2015-a. MRI-guided stereotactic amygdalohippocampectomy: a single center experience. Neuropsychiatr. Dis. Treat. 11, 359-74. Vojtěch, Z., Malíková, H., Syrůček, M., Krámská, L., Šroubek, J., Vladyka, V., Liščák R., 2015-b. Morphological changes after radiosurgery for mesial temporal lobe epilepsy. Acta Neurochir. (Wien) 157, 1783-91; discussion 1791-2.
Table 1: Engel Scores after SAHE
FU1 (n=39)
FU2 (n=39)
FU3 (n=39)
FU4 (n=39)
FU5 (n=39)
FU6 (n=39)
FU7 (n=34)
FU8 (n=26)
FU9 (n=25)
FU10 m(n=16)
FU11 (n=13)
FU12 (n=4)
Engel I
30 (77%)
32 (82%)
31 (79%)
30 (77%)
33 (84%)
33 (84%)
28 (82%)
22 (85%)
22 (88%)
13 (81%)
10 (77%)
4 (100%)
Engel II
6 (15%)
4 (10%)
4 (10%)
6 (15%)
2 (5%)
2 (5%)
2 (6%)
3 (11%)
2 (8%)
2 (12%)
2 (15%)
Engel III
2 (5%)
2 (5%)
3 (8%)
2 (5%)
3 (8%)
3 (8%)
3 (8%)
1 (5%)
1 (4%)
1 (6%)
1 (7%)
Engel IV
1 (3%)
1 (3%)
1 (3%)
1 (3%)
1 (3%)
1 (3%)
1 (3%)
S0920-1211(17)30229-2 http://dx.doi.org/10.1016/j.eplepsyres.2017.09.004 EPIRES 5804
To appear in:
Epilepsy Research
Received date: Revised date: Accepted date:
16-4-2017 27-6-2017 11-9-2017
Please cite this article as: Vojtˇech, Zdenˇek, Star´a, Michaela, An Epileptologist´es View: Seizure-related Outcomes after Radiofrequency Ablation for Mesial Temporal Lobe Epilepsy.Epilepsy Research http://dx.doi.org/10.1016/j.eplepsyres.2017.09.004 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
An Epileptologist´s View: Seizure-related Outcomes after Radiofrequency Ablation for Mesial Temporal Lobe Epilepsy Zdeněk Vojtěch, Michaela Stará Na Homolce Hospital Epilepsy Center; Prague, Czech Republic.
*
Corresponding author: Zdeněk Vojtěch, M.D, Ph.D.; Department of Neurology, Na Homolce
Hospital, Roentgenova 2, 150 30 Prague 5; E-mail address: [email protected] ; tel.+420 257272556; fax. +420 257273314
Highlights
SAHE destroys target structures only partially
In SAHE, seizure outcomes are comparable with open surgery
Seizure outcomes change only minimally over time
Summary In this article, we provide an overview of the reasons for the introduction of less invasive treatment modalities in the management of intractable mesial temporal lobe epilepsy (mTLE). We summarize our published research on stereotactic amygdalohippocampectomy (SAHE) and recalculate our data for the patients´ last visit. In our previous work, we found that patients achieved long-term seizurefree outcomes in 70.5%. Re-analysis of results in a subgroup of patient who were diagnosed and followed-up at Epilepsy Center, Na Homolce Hospital, Prague, indicate that these outcomes are
durable. Re-treatment in treatment failures was successful in all cases. The discussion compares novel treatment options and defines the place of SAHE among them. Key words Epilepsy surgery, stereotactic amygdalohippocampectomy, minimally invasive surgery
1. Introduction Surgical treatment of mTLE by anterior temporal lobectomy (ATL) or amygdalohippocampectomy (AHE) is an established treatment method which renders most of the patients to be seizure-free (60– 80%) (Spencer and Huh, 2008). Postoperative surgical morbidity is low with permanent deficits in less than 2% of patients in most centers (Georgiadis et al., 2013). Thus, what are the reasons for introducing stereotactic methods in the treatment of mTLE? Current surgical methods are based on the complete destruction of target structures (hippocampus, amygdala and parahippocampal gyrus). However, these operations frequently transect white matter tracts and resect tissue which is not epileptogenic. Several approaches have been developed to minimize collateral damage (transsylvian, subtemporal, and transcortical amygdalohippocampectomy) (Bozkurt et al., 2016). However, even these modifications could be the cause of it (eg. due to vascular spasms or direct white matter tracts transection). Paradoxically, there is a questionable correlation between the extent of resection and seizure outcome. This fact was demonstrated not only for the extent of neocortical temporal resections but also for hippocampal length/volume reduction (Schramm, 2008). Furthermore, the planned and real extent of the resection may differ (Schramm et al., 2011). In mTLE, epilepsy surgery is underutilized, largely because of concerns about its invasive nature and adverse side-effects which cause attending physicians to be reluctant to refer their patients for
surgery and for the patients to accept it (Englot et al., 2016). This is one of the reasons to search for less invasive treatment techniques which should be at least equally effective as treatment options used so far and have some advantage over these methods (safety profile, better patients´ comfort or cost effectiveness). In mTLE, despite a widely distributed epileptogenic network involving temporal and extratemporal structures, the epileptogenic zone is relatively circumscribed. Intuitively, one may think that a seizure outcome should be the same irrespective of the method by which mesiotemporal target structures are destroyed. Besides established epilepsy microsurgery, current literature offers several alternatives: multiple hippocampal transections, radiosurgery, laser ablation, MRI-guided focused ultrasound ablation and SAHE (Quigg and Harden, 2014).
2. Material and methods We performed SAHE over the period between 2004–2010 (Liščák et al., 2010).Then we stopped to practice it as an original stereotactic probe (Neuro N50, Fischer-Leibinger, Germany) became unavailable. Seizure outcomes have been discussed in previous articles. The problem with reporting these results is that patients from several institutions were referred for the treatment. Therefore, pre-surgical evaluation protocols and their interpretation varied. This led to inhomogeneity of the group. Furthermore, even patients followed-up at Epilepsy Center, Na Homolce Hospital, Prague frequently did not fulfil inclusion criteria for individual studies. Therefore, numbers of included patients in specific studies varied. A previous paper described the unselected group of all 61 treated patients (Vojtěch et al., 2014). Our preoperative diagnostics was based largely on standard noninvasive protocols (MRI, FDG-PET, scalp video-EEG, neuropsychological assessment) (Vojtěch et al., 2015-a). Noninvasive data (unilateral ictal pattern onset, hippocampal sclerosis and hypometabolism) were fully concordant in 36 and partially concordant or incomplete in 22 cases. We used intracranial video EEG recordings (SEEG) in three
cases. In three patients, another potentially epileptogenic lesion was found. Despite incomplete convergence of all preoperative tests, mTLE was diagnosed in all patients. 3. Results 3.1 Outcome with respect to seizures At the time of seizure outcome analysis, the mean postoperative follow-up was 5.3 years. We found Engel Class scores as follows: 43 (70.5 %) Class I, six (9.8 %) Class II, nine (14.8 %) Class III, and three (4.9 %) Class IV. For insufficient seizure control, five patients (8.2%) were reoperated on. Open surgery was performed in three patients in whom full coverage of the target structures was not possible due to individual anatomy. They all became Engel IA after the operation. Re-thermolesion was performed in two cases in whom the extent of the first lesion was suboptimal. One patient became Class IA, the other Class IB. No statistically significant difference was found in epilepsy duration and age at the time of the operation between seizure-free and non-seizure-free patients (Class I vs. Classes II-IV). Although data from a smaller subgroup showed a tendency for a better outcome in patients with concordant preoperative results and those treated on the left (Malíková et al., 2012), seizure outcomes did not differ in patients with completely and incompletely congruent preoperative data in the whole group. These results seem to change little over time. In one study we described 35 patients, (27 treated on the left and eight on the right) with a follow-up longer than one year (Malíková et al., 2012). One year after the procedure, Engel Classes were as follows: Class I in twenty-seven patients (77%), Class II in five patients (14%), Class III in one (3%) and Class IV in 2 (6%). 26 of these patients were followed-up for more than 3 years. 20 (77%) of them were Class I, three (12%) Class II, one Class III (4%), and two Class IV (8%).
For this article, Engel Scores were re-calculated in a subgroup of 39 patients who were diagnosed and treated at Epilepsy Center, Na Homolce Hospital, Prague, and in whom their last follow-up visit was less than one year (Table 1). Table 1: FU, follow-up visit (numbers= years after treatment) 28 of these patients were treated on the left and 11 on the right side. They were followed-up with for a mean of 8.83 years (106 months) (median 9 years [108 months]), range 5.4-12.2 years (65-146 months). 2 years after surgery their Engel Score was 32 Engel I (16 Engel IA), 4 Engel II, 2 Engel III, 1 Engel IV. All these patients were followed-up for 6 years. Their seizure outcome was as follows: 33 Engel I (18 Engel IA), 2 Engel II, 3 Engel III, 1 Engel IV. At their last visit, they were classified: 32 Engel I (20 Engel IA), 3 Engel II, 3 Engel III, 1 Engel IV. However, only three of 61 patients were not taking antiepileptic drugs. Seizures relapsed in the other five patients in whom treatment was attempted to be discontinued. In most patients the drug burden was at least reduced. 3.2 Neuroradiological results
Neuroradiological follow-up demonstrated only partial destruction of target structures which varied in size. Mean hippocampal volume reduction was 58±17% on the left and 54±27% on the right side (Malíková et al., 2012). In a small study of 18 patients, Engel Class IA was found in eight of nine patients (89%) in whom both amygdalar and hippocampal volumes were reduced by more than half (Malíková et al., 2009). In patients where both structures were destroyed by less than 50%, Engel Class I was 67%. In other studies, no convincing correlation was found between the seizure outcome and amygdalar and hippocampal volume reduction (Malíková et al., 2009, 2010). No significant correlation was found between the volume reduction of perirhinal and entorhinal cortices to seizure outcome (Malíková et al., 2011).
In a study of 75 mTLE patients (Malíková et al., 2014), seizure outcome after SAHE was compared (n=41, 11 on the right, 30 on the left) and ATL (n= 34, 21 on the right, 13 on the left ). Two years after surgery, the proportion of seizure-free patients was almost the same: 79.3% after SAHE and 76.5% after ATL. However, volume reductions were smaller in SAHE than ATL (amygdalar 50.3 ± 21.9% vs. 80.2 ± 20.9%, hippocampal 60.6 ± 18.7% vs. 86.0 ± 12.7%, respectively).
4. Discussion
The follow briefly compares the basic principles of current alternatives to conventional epilepsy surgery. Multiple hippocampal transections are a minimally destructive modification of traditional epilepsy surgery. Unfortunately, it has usually been used together with other methods (multiple subpial transections or topectomies) (Usami et al., 2016). Thus, the benefit of this method is difficult to assess. Furthermore, some collateral damage cannot be avoided in both access routestranssylvian (Uda et al., 2016) and trans middle temporal gyrus (Patil and Andrews, 2013). Major disadvantages of radiosurgery are delayed antiseizure effects, collateral damage and early and late radiotoxic changes which warrant prolonged neuroimaging follow-up (Vojtěch et al., 2015-b). On the other hand, laser therapy is highly targeted with minimal collateral damage and acts immediately. However, it destroys target structures in a confluent way, albeit incompletely. Reported results are somewhat inferior to open surgery and optimal volume of destruction is a matter of further research (Kang et al., 2016). The idea of SAHE is not new. It was performed in the 70´s using pneumoencephalography for navigation. Its seizure outcome was comparable to open surgery (Vladyka, 1978). Contemporary improvement of the method lies in application of modern neuroimaging and navigation methods (Liščák et al., 2010). SAHE has the potential advantages of minimal collateral damage, partial and non-confluent destruction of target structures, and immediate seizure control. We speculate that the antiepileptic effect of SAHE may be mediated by preferential disconnection of longitudinal hippocampal fibers
through which seizure activity spreads. The hypothesis is that some residual neuronal circuits may reorganize and support memory. Our idea is as follows – to achieve seizure reduction, it is important to balance volume reduction and confluency of the lesion. This issue comes from studies of the London-Ontario group (Parrent and Blume, 1999). In their article, the authors divided their patients into two groups. In Group I, they performed limited numbers of discrete lesions (mean, 6.4) in shorter anteroposterior length of amygdalohippocampal complex (13-21 mm, mean, 16.8 mm). In Group II, they created more lesions (mean, 26) in more confluent fashion and longer length (15-34 mm, mean, 21.5 mm). They achieved favorable outcome more often in Group II compared to Group I (60% vs. 20%). Our hypothesis is that better seizure outcome in our patients may be explained by wider coverage of amygdalohippocampal complex (16-38 lesions, median, 25, 30-45 mm trajectory, median, 35). We must stress that the results do not suggest that SAHE is superior to open epilepsy surgery in respect to seizure outcome. There is no reason why it should. Neither does this research comment on the differences in epileptological results of SAHE and other alternatives (eg. laser ablations). These questions warrant further studies comparing various methods. However, it is possible that patients may benefit from balancing between selectivity and minimization of collateral damage in the neuropsychological domain and receive better comfort. The direct costs of SAHE and conventional epilepsy surgery were not compared. However, the fact that no postoperative intensive care is needed in uncomplicated cases, and shorter stay in the hospital show that it should be more cost effective than open surgery. Furthermore, the stereotactic probe is obviously less expensive than equipment for laser ablation. A specific shortcoming of SAHE is the low percentage of drug-free patients. The disadvantage of all alternative methods is that no material for histologic evaluation is available. 5. Conclusion
Current experience with SAHE is limited. It is based on the results of a single center which treated a small and highly non-homogenous group of patients. There is also a bias as most patients were treated on the language dominant side. However, the promising results warrant further evaluation, ideally by a multicenter randomized study comparing SAHE with conventional surgery or other alternative treatment methods. Using contemporary neuroimaging technology, these studies may uncover certain patient groups which could benefit most from the treatment (eg. various types of hippocampal sclerosis or MRI-negative cases) or for which SAHE is not suitable (eg. mTLE plus). References Bozkurt, B., da Silva Centeno, R., Chaddad-Neto, F., da Costa, M.D., Goiri, M.A., Karadag, A., Tugcu, B., Ovalioglu, T.C., Tanriover, N., Kaya, S., Yagmurlu, K., Grande, A., 2016. Transcortical selective amygdalohippocampectomy technique through the middle temporal gyrus revisited: An anatomical study laboratory investigation. J Clin. Neurosci. 34: 237-45. Englot, D.J., 2013. The persistent under-utilization of epilepsy surgery. Epilepsy Res. 118, 68-9. Georgiadis, I., Kapsalaki, E.Z., Fountas, K.N., 2013. Temporal lobe resective surgery for medically intractable epilepsy: a review of complications and side effects. Epilepsy Res. Treat. 752195. Kang, J.Y., Wu. C., Tracy, J., Lorenzo, M., Evans, J., Nei, M., Skidmore, C., Mintzer, S., Sharan, A.D., Sperling, M.R., 2016. Laser interstitial thermal therapy for medically intractable mesial temporal lobe epilepsy. Epilepsia. 57, 325-34. Liščák, R., Malíková, H., Kalina, M., Vojtěch, Z., Procházka, T., Marusič, P., Vladyka, V, 2010. Stereotactic radiofrequency amygdalohippocampectomy in the treatment of mesial temporal lobe epilepsy. Acta Neurochir (Wien). 152(8):1291-8. Malíková, H., Krámská, L., Liščák, R., Vojtěch, Z., Procházka, T., Marečková, I., Lukavský, J., Druga, R., 2012. Stereotactic radiofrequency amygdalohippocampectomy for the treatment of temporal lobe epilepsy: do good neuropsychological and seizure outcomes correlate with hippocampal volume reduction? Epilepsy Res. 102, 34-44.
Malíková, H., Krámská, L., Vojtěch, Z., Liščák, R., Šroubek, J., Lukavský, J., Druga, R., 2014. Different surgical approaches for mesial temporal epilepsy: resection extent, seizure, and neuropsychological outcomes. Stereotact. Funct. Neurosurg. 92, 372-80. Malíková, H., Vojtěch, Z., Liščák, R., Procházka, T., Vymazal, J., Vladyka, V., Keller, J., Kalina, M., 2009. Stereotactic radiofrequency amygdalohippocampectomy for the treatment of mesial temporal lobe epilepsy: correlation of MR with clinical seizure outcome. Epilepsy Res. 83, 235-242. Patil, A., Andrews R., 2013. Long term follow-up after multiple hippocampal transection (MHT). Seizure. 22:731-4. Parrent, A. G., Blume, W. T., (1999). Stereotactic amygdalohippocampotomy for the treatment of medial temporal lobe epilepsy. Epilepsia. 1999;40(10):1408-16. Quigg, M., Harden, C., 2014. Minimally invasive techniques for epilepsy surgery: stereotactic radiosurgery and other technologies. J. Neurosurg. 121 Suppl., 232-40. Spencer, S., Huh, L., 2008. Outcomes of epilepsy surgery in adults and children. Lancet Neurol. 7, 52537. Schramm, J., 2008. Temporal lobe epilepsy surgery and the quest for optimal extent of resection: a review. Epilepsia 49, 1296-307. Schramm, J., Lehmann, T.N., Zentner, J., Mueller, C.A., Scorzin, J., Fimmers, R., Meencke, H.J., Schulze-Bonhage A., Elger, C.E., 2011. Randomized controlled trial of 2.5-cm versus 3.5-cm mesial temporal resection-Part 2: volumetric resection extent and subgroup analyses. Acta Neurochir. (Wien) 153, 221-8. Uda, T., Morino, M., Ito, H., Minami, N., Hosono, A., Nagai, T., Matsumoto, T., (2013). Transsylvian hippocampal transection for mesial temporal lobe epilepsy: surgical indications, procedure, and postoperative seizure and memory outcomes. J Neurosurg. 119:1098-104. Usami, K., Kubota, M., Kawai, K., Kunii, N., Matsuo, T., Ibayashi, K., Takahashi, M., Kamada, K., Momose, T., Aoki, S., Saito, N., 2016. Long-term outcome and neuroradiologic changes after multiple
hippocampal transection combined with multiple subpial transection or lesionectomy for temporal lobe epilepsy. Epilepsia. 57, 931-40. Vladyka, V., 1978. Tactics in the surgical treatment epilepsy and its realization in cases of temporal epilepsy. Cesk Slov Neurol N 41:95–106. Vojtěch, Z., Malíková, H., Krámská, L., Anýž, J., Syrůček, M., Zámečník, J., Liščák, R., Vladyka, V., 2014. Long-term seizure outcome after stereotactic amygdalohippocampectomy. Acta Neurochir. (Wien) 156, 1529-37. Vojtěch, Z., Malíková, H., Krámská, L., Liščák, R., Vladyka, V, 2015-a. MRI-guided stereotactic amygdalohippocampectomy: a single center experience. Neuropsychiatr. Dis. Treat. 11, 359-74. Vojtěch, Z., Malíková, H., Syrůček, M., Krámská, L., Šroubek, J., Vladyka, V., Liščák R., 2015-b. Morphological changes after radiosurgery for mesial temporal lobe epilepsy. Acta Neurochir. (Wien) 157, 1783-91; discussion 1791-2.
Table 1: Engel Scores after SAHE
FU1 (n=39)
FU2 (n=39)
FU3 (n=39)
FU4 (n=39)
FU5 (n=39)
FU6 (n=39)
FU7 (n=34)
FU8 (n=26)
FU9 (n=25)
FU10 m(n=16)
FU11 (n=13)
FU12 (n=4)
Engel I
30 (77%)
32 (82%)
31 (79%)
30 (77%)
33 (84%)
33 (84%)
28 (82%)
22 (85%)
22 (88%)
13 (81%)
10 (77%)
4 (100%)
Engel II
6 (15%)
4 (10%)
4 (10%)
6 (15%)
2 (5%)
2 (5%)
2 (6%)
3 (11%)
2 (8%)
2 (12%)
2 (15%)
Engel III
2 (5%)
2 (5%)
3 (8%)
2 (5%)
3 (8%)
3 (8%)
3 (8%)
1 (5%)
1 (4%)
1 (6%)
1 (7%)
Engel IV
1 (3%)
1 (3%)
1 (3%)
1 (3%)
1 (3%)
1 (3%)
1 (3%)
